Background Acute skeletal muscle wasting may predict clinical outcomes in critically ill patients. This study aimed to assess acute muscle loss, changes in anthropometric measurements, and the relationship between muscle loss and clinical outcomes in critically ill trauma and surgical patients. Methods This single-center, prospective observational study was conducted in critically ill trauma and surgical patients who were expected to stay in the intensive care unit (ICU) for at least 7 days. Rectus femoris cross-sectional area muscle measurements were performed by bedside ultrasound, and anthropometric measurements were obtained at baseline and 7 days after the first assessment. Length of mechanical ventilation, ICU and hospital stay, and mortality were recorded. Results Thirty-five patients with a mean age of 49.6 +/- 18.6 years and 74.1% male were enrolled. The rectus femoris cross-sectional area, mid-arm circumference, and calf circumference were reduced at second assessment from baseline (P < 0.05). In univariate analysis, muscle loss and changes in anthropometric measurements were not associated with 90-day mortality (P > 0.05). Conclusion Muscle loss in critical trauma and surgical patients occurred rapidly during the first week of critical illness. Rectus femoris muscle cross-sectional area assessment can be used to detect skeletal muscle changes in critically ill patients. Further investigations on the skeletal muscle changes and clinical outcomes need to be conducted.